In mammals, protein kinase C (hereinafter referred to as “PKC”) is a family consisting of 12 isoforms, and it is known to be a serine-threonine kinase that takes part in signal transduction. In addition to this, PKC is known to be involved in regulating various cell functions such as synaptic transmission, ion flux activation, secretion, cell cycle control, differentiation, multiplication, tumorigenesis, metastasis, and apoptosis. Compounds having PKC activity enhancing effect (hereinafter referred to as “PKC activity enhancers”) are known to have, for example, an ameliorating effect on glucose metabolism disorder in liver cirrhosis animal models (NON-PATENT DOCUMENT 1), and an antineoplastic effect (NON-PATENT DOCUMENT 2). PKC activity enhancers are drawing much attention as therapeutic agents against various diseases, for example, glucose metabolism disorders in liver cirrhosis patients, and neoplastic diseases such as tumors.
For example, leucine is known to be PKC activity enhancer (NON-PATENT DOCUMENT 3). Branched chain amino acids (leucine and isoleucine in particular), used in branched chain amino acid replacement therapy for liver cirrhosis patients, activate PKC through PI3 kinase, promote glucose uptake by skeletal muscles, and also ameliorate glucose metabolism disorders in the liver cirrhosis rat model (NON-PATENT DOCUMENT 1).
For example, bryostatin and gnidimacrin are also known as PKC activity enhancers. Bryostatin binds to PKC (NON-PATENT DOCUMENT 4), activates PKC isozymes in vitro (NON-PATENT DOCUMENT 5), and shows antineoplastic effect (NON-PATENT DOCUMENT 6).
The alkyl ether derivatives described in the present application have been reported to have nerve protective activity, nerve regenerative activity, and neurite outgrowth promoting activity (Patent document 1). However, it is not known so far that they enhance PKC activity.    PATENT DOCUMENT 1: WO 03/035647    NON-PATENT DOCUMENT 1: Am. J. Physiol. Gastrointest. Liver. Physiol., 2005, Vol. 288, p. G1292-1300    NON-PATENT DOCUMENT 2: Curr. Cancer Drug Targets, 2004, Vol. 4, p. 125-146    NON-PATENT DOCUMENT 3: Biochem. Biophys. Res. Commun., 2002, Vol. 299, No. 5, p. 693-696    NON-PATENT DOCUMENT 4: Biochem. Pharmacol., 1992, Vol. 43, No. 9, p. 2007-2014    NON-PATENT DOCUMENT 5: Mol. Pharmacol., 1994, Vol. 46, No. 2, p. 374-379    NON-PATENT DOCUMENT 6: Rev. Physiol. Biochem. Pharmacol., 2001, Vol. 142, p. 1-96